65 research outputs found

    Identification and characterization of an endogenous chemotactic ligand specific for FPRL2

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    Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein–coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal–regulated kinase 1/2 mitogen-activated protein kinases through the Gi class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2

    Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

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    French Hospital Database on HIVInternational audienceBackgroundThe effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals.MethodsPatients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated.ResultsAmong 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights.ConclusionThe impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population

    Impact of Low-Level-Viremia on HIV-1 Drug-Resistance Evolution among Antiretroviral Treated-Patients

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    to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART).Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before.48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients.Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting

    Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

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    La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

    LES COMPLICATIONS DE LA LIPOLYSE ULTRASONIQUE (A PROPOS DE TROIS CAS DE BRULURES DRAMATIQUES)

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    STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    Complications du laser resurfacing dans le traitement du vieillissement du visage

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    TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    Barreira cutânea para reconstrução mamária com prótese Dermal barrier for immediate prosthetic breast reconstruction

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    INTRODUÇÃO: A reconstrução mamária imediata com implante de silicone após mastectomia subcutânea tornou-se uma opção válida para médicos e pacientes devido à simplicidade das manobras cirúrgicas, menor tempo cirúrgico, cicatriz mínima e resultados estéticos imediatos. Os implantes submusculares também são recomendados, apesar de exigirem um procedimento cirúrgico mais agressivo. Ambos também podem causar problemas secundários que já foram descritos. Para reduzir esse tipo de problemas, neste artigo é descrita uma modificação da mastopexia circunvertical, redução do padrão de mamoplastia para mastectomia e a reconstrução mamária imediata com implante. MÉTODO: A pele entre as linhas de incisão cutânea medial e vertical lateral é desepitelizada, criando uma barreira cutânea para a prótese para reforçar a linha de sutura vertical. CONCLUSÕES: A técnica garante uma reconstrução segura, com resultados estéticos gratificantes.BACKGROUND: Immediate breast reconstruction with silicone implant after subcutaneous mastectomy became a valid option among doctors and patients based on the simplicity of the surgical maneuvers, shorter surgical period, minimal scarring and immediate aesthetic results. Submuscular implants also have been advocated despite its more aggressive surgical procedures. Both also may bring secondary already described diversification's problems. An in attempt to reduce this kind of problems, in this article, a modification of the circumvertical mastopexy, reduction mammoplasty pattern for mastectomy and immediate breast implant reconstruction is described. METHODS: The skin between the medial and lateral vertical skin incision lines is de-epithelialized, providing a dermal barrier over the prosthesis to reinforce the vertical suture line. CONCLUSIONS: The technique ensures a safe reconstruction with gratifying aesthetic results

    Can HIV epidemics among men who have sex with men be eliminated through participation in PrEP rollouts?

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    International audienceObjectives: To study the conditions under which PrEP coverage can eliminate HIV among men who have sex with men (MSM) in the Paris region.Design: Mathematical modeling.Methods: We propose an innovative approach, combining a transmission model with a game-theoretic model, for decision-making about PrEP use. Individuals at high risk of HIV infection decide to use PrEP, depending on their perceived risk of infection and the relative cost of using PrEP versus antiretroviral treatment (ART), which includes monetary and/or non-monetary aspects, such as price and access model of PrEP, consequences of being infected and lifelong ART.Results: If individuals assessed correctly their infection risk, and the cost of using PrEP were sufficiently low, then the PrEP rollout could lead to elimination. Specifically, assuming 86% PrEP effectiveness, as observed in two clinical trials, a minimum PrEP coverage of 55% (95% CI:43%–64%) among high-risk MSM would achieve elimination in the Paris region. A complete condom drop by MSM using PrEP slightly increases the minimum PrEP coverage required for elimination, by ∼1%, while underestimation of their own HIV infection risk would require PrEP programs reduce the cost of using PrEP by a factor ∼2 to achieve elimination.Conclusions: Elimination conditions are not yet met in the Paris region, where at most 47% of high-risk MSM were using PrEP as of mid-2019. Further lowering the cost of PrEP and promoting a fair perception of HIV risk are required and should be maintained in the long run, to maintain elimination status
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